Wavelet analysis in infantile nystagmus syndrome: limitations and abilities.

Purpose: To investigate the proper usage of wavelet analysis in infantile nystagmus syndrome (INS) and determine its limitations and abilities.

Methods: Data were analyzed from accurate eye-movement recordings of INS patients. Wavelet analysis was performed to examine the foveation characteristics, morphologic characteristics and time variation in different INS waveforms.

From infectious diseases to primary immunodeficiencies.

The field of primary immunodeficiencies has expanded, thanks to the exploration of novel clinical phenotypes and their connection with morbid genotypes, and the subsequent exploration of new patients who have known primary immunodeficiency-defining clinical phenotypes and their connection with novel morbid genotypes. This two-way process is becoming increasingly active, particularly for patients who have infectious diseases in whom the underlying immunologic and genetic causes remain mostly unexplained. The authors review how the exploration of children who have clinical infectious diseases caused by mycobacteria, pneumococcus, and herpes simplex virus recently led to the description of three new groups of primary immunodeficiencies.

Factors influencing the experience of oscillopsia in infantile nystagmus syndrome.

Purpose: Perceptual instability in infantile nystagmus syndrome (INS) has been reported occasionally. This study was conducted to examine the factors that influence perceptual stability in 18 individuals with INS.

Methods: The subjects were instructed to look continuously at a fixation LED centered in an image (38 degrees x 32 degrees ) at two luminance levels (3.

A functional promoter variant in IL12B predisposes to cerebral malaria.

The role of the Th1 pathway in the pathogenesis of severe malaria is unclear. We recently reported that a polymorphism with increasing IFNG transcription is associated with protection against cerebral malaria (CM). Interleukin-12 is required for Th1 cell differentiation, which is characterized by the production of interferon-gamma.

Task-induced stress and motivation decrease foveation-period durations in infantile nystagmus syndrome.

Purpose: To investigate the effect of visual demand, task-related physiological stress, and motivation on the nystagmus waveform of 19 subjects with infantile nystagmus syndrome (INS).

Methods: Subjects viewed a Landolt C of varying orientation and size, and indicated its orientation via arrow keys on a keyboard. Mental arithmetic was performed in conjunction with the visual task.

A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo.

Natural killer (NK) cells have been originally defined by their "naturally occurring" effector function. However, only a fraction of human NK cells is reactive toward a panel of prototypical tumor cell targets in vitro, both for the production of interferon-gamma (IFN-gamma) and for their cytotoxic response. In patients with IL12RB1 mutations that lead to a complete IL-12Rbeta1 deficiency, the size of this naturally reactive NK cell subset is diminished, in particular for the IFN-gamma production.

Evaluation of a model for efficient screening of tuberculosis contact subjects.

Rationale: Contact tracing is an important component of tuberculosis (TB) control programs. Standardization of contact investigation protocols can make them more efficient.

Objectives: To develop a model to select contact subjects for screening.

Leprosy as a genetic model for susceptibility to common infectious diseases.

Leprosy (Hansen's disease) is a human infectious disease that can be effectively treated with long-term administration of multi-drug therapy. In 2006, over 250,000 new cases were reported to the World Health Organization. In the nineteenth century, disagreement among leprologists regarding the hereditary or infectious nature of leprosy was resolved with the identification of the etiological agent, Mycobacterium leprae.

PSA spike after brachytherapy For localized prostate cancer.

A common concern for patients who have undergone treatment for prostate cancer and their families is an elevation or spike in the PSA level following definitive treatment. A number of factors can be responsible for this, but often the PSA spike may be benign. An informed health care worker can reasonably assess whether this is the case, and can help to alleviate the fears of the patient and his family.

Novel primary immunodeficiencies revealed by the investigation of paediatric infectious diseases.

Human primary immunodeficiencies impairing myeloid and/or lymphoid cellular responses to activating receptors other than antigen receptors have recently been described in children with various infectious diseases. Germline mutations in NEMO and IKBA impair NF-kappaB-mediated signalling, at least in response to the stimulation of TLRs, IL-1Rs and TNFRs, and confer a broad predisposition to infections. Mutations in IRAK4 selectively impair TLRs other than TLR3 and most IL-1R responses, and confer a predisposition to pyogenic bacterial diseases, including invasive pneumococcal disease in particular.

Oscillopsia in "inverse latent" infantile nystagmus syndrome.

Purpose: A possibly unique individual with infantile nystagmus syndrome presented with incessant oscillopsia but good stereopsis when viewing binocularly; her nystagmus was greatly reduced with left eye occlusion. We have attempted to explain this and to identify an intervention that preserves binocular vision while maximizing perceptual stability.

Case Report And Methods: Eye movements were recorded and analyzed for duration of foveation (% time when the target was on or near the fovea and the eye was moving at < or = 4 degrees /sec) under different viewing conditions.

Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans.

Purpose Of Review: Herpes simplex encephalitis is a rare complication of herpes simplex virus 1 infection that strikes otherwise healthy individuals. Its pathogenesis has long remained elusive. We highlight the investigations dealing with the genetic basis of herpes simplex encephalitis in mice and humans.

Human Toll-like receptor-dependent induction of interferons in protective immunity to viruses.

Five of the 10 human Toll-like receptors (TLRs) (TLR3, TLR4, TLR7, TLR8, and TLR9), and four of the 12 mouse TLRs (TLR3, TLR4, TLR7, TLR9) can trigger interferon (IFN)-alpha, IFN-beta, and IFN-lambda, which are critical for antiviral immunity. Moreover, TLR3, TLR7, TLR8, and TLR9 differ from TLR4 in two particularly important ways for antiviral immunity: they can be activated by nucleic acid agonists mimicking compounds produced during the viral cycle, and they are typically present within the cell, along the endocytic pathway, where they sense viral products in the intraluminal space. Investigations in mice have demonstrated that the TLR7/9-IFN and TLR3-IFN pathways are different and critical for protective immunity to various experimental viral infections.

Genomewide linkage analysis of the granulomatous mitsuda reaction implicates chromosomal regions 2q35 and 17q21.

The Mitsuda reaction, a delayed granulomatous skin reaction elicited by the intradermal injection of heat-killed Mycobacterium leprae, is an in vivo test reflecting the ability to generate an immune granuloma after sensitization by diverse mycobacterial infections. Accumulating evidence for the genetic control of the Mitsuda reaction has been reported. We performed a genomewide linkage scan for the quantitative Mitsuda reaction in 19 large families from Vietnam with a history of leprosy (114 offspring).

Immunology in natura: clinical, epidemiological and evolutionary genetics of infectious diseases.

The field of human genetics of infectious diseases defines the genes and alleles rendering individuals (clinical genetics) and populations (epidemiological genetics) vulnerable to infection, and studies those selected by previous infections (evolutionary genetics). These disciplines--clinical, epidemiological and evolutionary genetics-delineate the redundant and nonredundant functions of host defense genes for past and present survival in natura--in natural ecosystems governed by natural selection. These disciplines, in other words, assess the ecologically relevant and evolutionarily selected roles of human genes and alleles in protective immunity to diverse and evolving microorganisms.

Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity.

Human interleukin (IL) 1 receptor-associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3- and TLR4-interferon (IFN)-alpha/beta pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK-4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines.

TLR3 deficiency in patients with herpes simplex encephalitis.

Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves.

Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study.

Background: Niemann-Pick type C disease (NPC) is an inherited neurodegenerative disorder characterised by an intracellular lipid-trafficking defect with secondary accumulation of glycosphingolipids. Miglustat, a small iminosugar, reversibly inhibits glucosylceramide synthase, which catalyses the first committed step of glycosphingolipid synthesis. Miglustat is able to cross the blood-brain barrier, and is thus a potential therapy for neurological diseases.

Primary immunodeficiencies: a field in its infancy.

A paradigm shift is occurring in the field of primary immunodeficiencies, with revision of the definition of these conditions and a considerable expansion of their limits. Inborn errors of immunity were initially thought to be confined to a few rare, familial, monogenic, recessive traits impairing the development or function of one or several leukocyte subsets and resulting in multiple, recurrent, opportunistic, and fatal infections in infancy. A growing number of exceptions to each of these conventional qualifications have gradually accumulated.

Human primary immunodeficiencies of type I interferons.

Type I interferons (IFN-alpha/beta and related molecules) are essential for protective immunity to experimental infection by numerous viruses in the mouse model. In recent years, human primary immunodeficiencies affecting either the production of (UNC-93B deficiency) or the response to (STAT1 and TYK2 deficiencies) these IFNs have been reported. Affected patients are highly susceptible to certain viruses.

Human monogenic disorders that confer predisposition to specific infections.

Human monogenic disorders affecting immunity to infection are increasingly recognized. Most are associated with primary immunodeficiencies, which typically confer predisposition to multiple infectious diseases. We review here the known, atypical monogenic disorders that confer a narrow vulnerability to infection with specific microorganisms in otherwise healthy individuals.

Host genetics of mycobacterial diseases in mice and men: forward genetic studies of BCG-osis and tuberculosis.

In humans, genetic factors have long been suspected to contribute to the onset and outcome of tuberculosis. Such effects are difficult to identify owing to their complex inheritance, and to the confounding impact of environmental factors, notably pathogen-associated virulence determinants. Recently, forward genetic approaches in mouse models and in human populations have been used to elucidate a molecular basis for predisposition to mycobacterial diseases.

Association of killer cell immunoglobulin-like receptor genes with Hodgkin's lymphoma in a familial study.

Background: Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells.

Mycobacterial infections: PARK2 and PACRG associations in leprosy.

An overview of investigations indicating an important role of host genetics, both major histocompatibility complex (MHC) and non-MHC, in leprosy.